Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000277.2(PAH):c.464G>C (p.Arg155Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229561

102687 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a532eae1-862f-4d90-b69e-5e590a9f7512

Approved on: 2018-08-10

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.464G>C

NM_000277.2(PAH):c.464G>C (p.Arg155Pro)

NC_000012.12:g.102866641C>G

CM000674.2:g.102866641C>G

NC_000012.11:g.103260419C>G

CM000674.1:g.103260419C>G

NC_000012.10:g.101784549C>G

NG_008690.1:g.55962G>C

NG_008690.2:g.96770G>C

NM_000277.1:c.464G>C

NM_001354304.1:c.464G>C

NM_000277.3:c.464G>C

ENST00000307000.7:c.449G>C

ENST00000549111.5:n.560G>C

ENST00000551988.5:n.530+10821G>C

ENST00000553106.5:c.464G>C

Likely Pathogenic

PP3 PM3 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PM2: absent from ExAC, gnomAD, 1000G, ESP. PAGE MAF=0.00066; PP3: Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.967; PP4_Moderate: Detected in a patient with classic PKU. Cofactor deficiency excluded. (PMID:10679941); PM3: Detected in trans with R408W (P) (PMID:10679941). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PP4_Moderate, PM3).

PP3

Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.967

PM3

Detected in trans with R408W (P)

Detected in trans with R408W PubMed:10679941

PM2

absent from ExAC, gnomAD, 1000G, ESP. PAGE MAF=0.00066

PP4_Moderate

Detected in a patient with classic PKU. Cofactor deficiency excluded.

302 PKU or HPA patients in 290 families were analyzed. Most of the patients were identified by neonatal screening. Cofactor deficiency was excluded by the BH4 test. Detected in a patient (SD) with classic PKU. PubMed:10679941

Curation History

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